Zika virus infection downregulates MHC class I presentation

Abstract

Nucleated cells express major histocompatibility complex class I (MHC-I), which presents antigens for CD8+ T cells to recognize and eliminate infected cells. Therefore, many viruses have evolved strategies to downregulate MHC-I for the purpose of immune evasion. However, current evidence on the effect of Zika virus (ZIKV) infection on MHC-I presentation is conflicting. Whether ZIKV interferes with the process of antigen presentation remains elusive. In the present study, I found that ZIKV infection downregulates MHC-I surface expression in microglial cells and astrocytic cells in both the infected and uninfected bystander subpopulations. In addition, infection failed to activate microglia and trigger pro-inflammatory cytokine secretion. Activation of monocytes and their antigen presentation during infection were also minimal. Our results indicate that MHC-I is likely degraded during ZIKV infection in a proteasome-independent manner. Using a quantitative proteomics approach to isolate activated E3-ligases from ZIKV-infected CD14+ monocytes, we identified MARCH2 and MARCH9. Given the previously implicated interactions of these E3-ligases with MHC-I, our results suggest their possible role in MHC-I degradation via the autophagy or lysosomal pathways. Taken together, my study has shown the ability of ZIKV in limiting antigen presentation to suppress T cell responses. These results provide fundamental insights into why ZIKV is well-adapted to replicate in monocytes and the brain, and may provide necessary understanding for vaccine and therapy development against ZIKV.